Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome

• DOI: 10.1126/science.1233151
• Publication Date: 2013-07-12T04:54:00Z
• Authors: Alessandro Aiuti; Luca Biasco; Samantha Scaramuzza; Francesca Ferrua; Maria Pia Cicalese; Cristina Baricordi; Francesca Dionisio; Andrea Calabria; Stefania Giannelli; Maria Carmina Cas...; Marita Bosticardo; Costanza Evangelio; Andrea Assanelli; Miriam Casiraghi; Sara Di Nunzio; Luciano Callegaro; Claudia Benati; Paolo Rizzardi; Danilo Pellin; Clelia Di Serio; Manfred Schmidt; Christof Von Kalle; Jason Gardner; Nalini Mehta; Victor Neduva; David J. Dow; Anne Galy; Roberto Miniero; Andrea Finocchi; Ayse Metin; Pinaki P. Banerjee; Jordan S. Orange; Stefania Galimberti; Maria Grazia Vals...; Alessandra Biffi; Eugenio Montini; Anna Villa; Fabio Ciceri; Maria Grazia Ronc...; Luigi Naldini
• Keywords: Wiskott–Aldrich syndrome; Hematopoietic stem cell

Wiskott-Aldrich syndrome (WAS) is an inherited immunodeficiency caused by mutations in the gene encoding WASP, a protein regulating cytoskeleton. Hematopoietic stem/progenitor cell (HSPC) transplants can be curative, but, when matched donors are unavailable, infusion of autologous HSPCs modified ex vivo therapy alternative approach. We used lentiviral vector functional WASP to genetically correct from three WAS patients and reinfused cells after reduced-intensity conditioning regimen. All showed stable engraftment WASP-expressing improvements platelet counts, immune functions, clinical scores. Vector integration analyses revealed highly polyclonal multilineage haematopoiesis resulting gene-corrected HSPCs. Lentiviral did not induce selection integrations near oncogenes, no aberrant clonal expansion was observed 20 32 months. Although extended observation required establish long-term safety, represents promising treatment for WAS.